Generic Name

Doxepin

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Classification

FDA Approved Indications

• Depressive disorder
• Insomnia (Silenor)
• Pruritus (Zonalon)

Mechanism of Action

Doxepin works by inhibiting the reuptake of serotonin and norepinephrine in the central nervous system, thereby increasing their levels to exert antidepressant effects. It also has antihistamine properties contributing to its sedative effects.

Dosage and Administration

Adult: Depression: 75-150 mg/day divided into doses. Insomnia (Silenor): 3-6 mg at bedtime. Pruritus (Zonalon): Apply thin layer to affected area once daily.

Pediatric: Not typically used in children for depression; specific dosing for insomnia or pruritus should be prescribed by a healthcare provider.

Geriatric: Start at lower doses due to increased sensitivity, typically 25-50 mg at bedtime.

Renal Impairment: Use caution; dose adjustments may be necessary.

Hepatic Impairment: Use with caution; dose may need to be reduced.

Pharmacokinetics

Absorption: Well absorbed orally with high bioavailability.

Distribution: Widely distributed in body tissues, crosses the blood-brain barrier.

Metabolism: Metabolized in the liver mainly by CYP2D6, CYP1A2, and other CYP enzymes.

Excretion: Excreted mainly in urine as metabolites, minor amount unchanged in urine.

Half Life: Approximately 8-24 hours, variable depending on individual metabolism.

Contraindications

• Hypersensitivity to doxepin or other TCAs.
• Recent myocardial infarction.
• Use with caution in narrow-angle glaucoma, urinary retention, monoamine oxidase inhibitors (MAOIs).

Precautions

• Use with caution in elderly, patients with cardiac disease, arrhythmias, seizure history, or bipolar disorder. Monitor for suicidal ideation, especially in young adults. Pregnancy and lactation should be discussed with healthcare provider.

Adverse Reactions - Common

• Drowsiness (Frequent)
• Dizziness (Frequent)
• Dry mouth (Frequent)
• Weight gain (Less common)

Adverse Reactions - Serious

• Cardiac conduction abnormalities (Rare)
• Seizures (Rare)
• Suicidal thoughts (Monitor closely in early therapy)
• Serotonin syndrome (Rare, especially if combined with other serotonergic agents)

Drug-Drug Interactions

• MAOIs (risk of serotonin syndrome)
• Other CNS depressants (enhanced sedation)
• QT prolonging agents (risk of arrhythmias)
• Cimetidine (may increase doxepin levels)

Drug-Food Interactions

• Alcohol (enhanced CNS depression)

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Take medication exactly as prescribed. Do not stop abruptly. Avoid alcohol and other CNS depressants.
• Be aware of potential side effects like drowsiness, dry mouth, and dizziness.
• Report worsening mood, suicidal thoughts, or unusual side effects to healthcare provider.

Special Considerations

Black Box Warnings:

• Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults with depression.

Genetic Factors: CYP2D6 poor metabolizers may have increased drug levels.

Lab Test Interference: May interfere with certain thyroid function tests.

Overdose Management

Signs/Symptoms: Confusion, hallucinations, seizures, arrhythmias, coma, death.

Treatment: Supportive care, activated charcoal if recent ingestion, monitoring cardiac function, and symptomatic treatment. Consider consultation with poison control or medical toxicology.

Storage and Handling

Storage: Store at room temperature, away from light and moisture.

Stability: Stable under normal conditions; check specific product details.